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Stomach endoscopy 3 (Photo credit: Wikipedia)

Are autism, gut inflammation, and immune issues linked? One recent sponsored supplementpublished in the journal Pediatrics argues that they are. There's certainly some evidence, although quite mixed, hinting at a link between immune or gut issues and a subset of people with autism, although which one triggers the other is nowhere near resolved. What one might hope is resolved is that it's difficult to construct solid scientific arguments on a shaky foundation that incorporates retracted papers.

The Pediatrics GI-autism supplement reflects information derived from a symposium conducted in 2009, one convened to talk about GI problems and autism. The authors are recognizable as those whose interest has very much been focused on autism as inflammation, particularly gut inflammation. The problem has been pinning down specifically what that inflammation might be and where it occurs. To demonstrate that such evidence has been identified, the authors write:

Endoscopic analyses of children with ASD and GI symptoms have revealed the presence of a subtle, diffuse inflammation of the intestinal tract (reviewed in refs 9 and 25). Characterizing the nature of this inflammation remains an area in need of further investigation to fully understand and to provide further evidence of its relationship to GI symptoms in individuals with ASDs.

I've followed the studies on GI and autism, in part out of curiosity and in part out of a confirmation bias because our autistic son had gut problems early on (that he no longer has) while our youngest, non-autistic son has persistent GI complaints. My general impression has been that data confirm some heightened gut issues related to constipation and anxiety, although one large, 30-year study found no link at all between GI disease and autism. Some research suggests autism-specific pathways involved in children who do have GI problems. But results from study to study are mixed and yield a fuzzy picture. Even the data on the microbiome--the microbial inhabitants of the intestinal tract whose identity and numbers can influence health--are in conflict, as they are for whether or not specific autistic behaviors or severity can indicate underlying GI problems.

Indeed, study findings show a huge variation in percentages of autistic people with reported GI problems and how they compare to those without autism, as this graph illustrates. Of course, each study given in that graph had a different population with different numbers and probably variable versions of autism, so no one can say firmly what the frequency of GI problems really is among autistic people.

One impression I had, though, is that there's a dearth in the scientific findings of intestinal clinical signs, such as from endoscopy, in autistic people, which has made it rather difficult to establish any definitive link. Some clinical findings point to esophageal dysfunction: one study found more reflux in autistic children, another identified a rare esophogeal disorder associated with three cases of autism, and yet another found esophageal dysfunction in girls and women with Rett syndrome, a genetic form of autism. Another option for explaining at least some GI problems in autism is a non-infectious, non-inflammatory cause linked to misfires of the enteric nervous system, the 'little brain' that resides in your abdomen as a multiplex of nerves that indeed sometimes seem to have a mind of their own. But confirmatory endoscopic evidence for the lower gut is scant, as far as I knew. So when I read that above quote about endoscopic analyses showing a "subtle, diffuse inflammation" in the intestinal tract, my first thought was, "Eh?" It's a compelling and confident statement of a link between gut inflammation and autism, but what is the evidence?

So, I looked at references 9 and 25, cited in the quote above. As the parenthetical says, they are reviews. Reference 9 is a consensus statement published in Pediatrics in 2010. I searched it for mentions of inflammation and endoscopy. First, I note that it says the following about GI disorders and autism:

The existence of a gastrointestinal disturbance specific to persons with ASDs (eg, “autistic enterocolitis”) has not been established

and

The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs.

Referencing the findings of gut inflammation, this 2010 review says:

Researchers in a number of laboratories have described intestinal inflammatory changes in individuals with ASDs

and cites three references, 59, 60, and 61.

Note that this consensus statement was published just before The Lancet retracted the infamous 1998 Wakefield et al. paper that set off the whole treacherous distraction of "vaccines cause autism." In fact, it cites that paper, although discussing it with a critical eye.